Derivatives of certain pyridyliminomethyl-benzenes

ABSTRACT

Derivatives of certain pyridyliminomethylbenzenes, useful as fungicides.

This is a division of application Ser. No. 228,427, filed Jan. 26, 1981,which was a continuation of application Ser. No. 130,681, filed Mar. 17,1980, abandoned. Application Ser. No. 228,427 has issued as U.S. Pat.No. 4,355,035.

DESCRIPTION OF THE INVENTION

This invention relates to certain derivatives ofpyridyliminomethylbenzenes, these derivatives being described by theformula: ##STR1## wherein X is alkoxy, haloalkoxy, alkylthio of from oneto six carbon atoms; m is 1 or 2; and Y is halogen.

The pyridyliminomethylbenzenes of Formula I form acid-addition salts,for example, salts of hydrohalic acids, particularly of hydrochloricacid, or of sulfuric acid. Such salts are also of interest as having thefungicidal activity of the pyridyliminomethylbenzenes from which theyare formed (in a manner well known per se), and, accordingly, areincluded within the scope of the present invention. It is also notedthat the salt should be non-phytotoxic (which can readily be determinedby routine test), since normally this is a requirement of fungicidalcompositions.

Preferred halogen substituents are chlorine, fluorine and bromine atoms,chlorine being particularly preferred.

Preferred compounds of the invention are those wherein m is one and thesubstituent Y is attached at the 4-position of the benzene ring.Preferably, (Y)_(m) is 4-chloro, as, for example, in a preferredcompound: 4-chloro-(3'-pyridyl)-imino-C-(isobutylthio)methylbenzene.

However, compounds in which (Y)_(m) represents di-halo substitution arealso particularly effective. In such case (Y)_(m) is preferablydichloro-, and advantageously the chlorine atoms are in the 2,4- or3,4-positions of the benzene ring.

The compounds of the invention can be prepared by treating a compound ofthe general formula: ##STR2## with a compound of the formula

    Q--X

wherein Q is hydrogen or an alkali metal atom, optionally in thepresence of an acid acceptor.

The intermediates of formula II are conveniently prepared by reacting athionyl halide with the appropriate N-(3'-pyridyl)benzamide of thegeneral formula: ##STR3##

Compounds of Formula I can also be prepared by alkylation of thecorresponding thioanilides.

The compounds of formula I have been found to exhibit fungicidalproperties.

Accordingly, the invention further provides a fungicidal compositioncomprising a compound of formula I as defined above in association withat least one inert carrier therefor, and a method of making such acomposition which comprises bringing a compound of formula I as definedabove into association with at least one inert carrier therefor.

Further in accordance with the invention there is provided a method ofprotecting a crop fungal attack comprising treating crops subject to orsubjected to fungal attack, seeds of such crops or soil in which suchcrops are growing or are to be grown with a compound of formula I or acomposition according to the invention.

A carrier in a composition according to the invention is any materialwith which the active ingredient is formulated to facilitate applicationto the locus to be treated, which may, for example, be a plant, seed orsoil, or to facilitate storage, transport or handling. A carrier may bea solid or a liquid, including a material which is normally gaseous butwhich has been compressed to form a liquid, and any of the carriersnormally used in formulating fungicidal compositions may be used.

Suitable solid carriers include natural and synthetic clays andsilicates, for example, natural silicas such as diatomaceous earths;magnesium silicates, for example, talcs; magnesium aluminum silicates,for example, attapulgites and vermiculities; aluminum silicates, forexample, kaolinites, montmorillonites and micas; calcium carbonate;calcium sulfate; synthetic hydrated silicon oxides and synthetic calciumor aluminum silicates; elements, for example, carbon and sulfur; naturaland synthetic resins, for example, coumarone resins, polyvinyl chloride,and styrene polymers and copolymers; solid polychlorophenols; bitumen;waxes, for example, beeswax, paraffin wax, and chlorinated mineralwaxes; and solid fertilizers, for example, superphosphates.

Suitable liquid carriers include water; alcohols, for example,isopropanol and glycols; ketones, for example, acetone, methyl ethylketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic oraraliphatic hydrocarbons, for example, benzene, toluene and xylene;petroleum fractions, for example, kerosine and light mineral oils;chlorinated hydrocarbons, for example, carbon tetrachloride,perchloroethylene and trichloroethane. Mixtures of different liquids areoften suitable.

Fungicidal compositions are often formulated and transported in aconcentrated form which is subsequently diluted by the user beforeapplication. The presence of small amounts of a carrier which is asurface-active agent facilitates this process of dilution. Thus,preferably, at least one carrier in a composition according to theinvention is a surface-active agent. For example, a composition maycontain at least two carriers, at least one of which is a surface-activeagent.

A surface-active agent may be an emulsifying agent, a dispersing agentor a wetting agent; it may be nonionic or ionic. Examples of suitablesurface-active agents include the sodium or calcium salts of polyacrylicacids and lignin sulfonic acids; the condensation products of fattyacids or aliphatic amines or amides containing at least 12 carbon atomsin the molecule with ethylene oxide and/or propylene oxide; fatty acidesters of glycerol, sorbitan, sucrose or pentaerythritol; condensates ofthese with ethylene oxide and/or propylene oxide; condensation productsof fatty alcohol or alkyl phenols, for example, p-octylphenol orp-octylcresol, with ethylene oxide and/or propylene oxide; sulfates orsulfonates of these condensation products; alkali or alkaline earthsalts, preferably sodium salts, of sulfuric or sulfonic acid esterscontaining at least 10 carbon atoms in the molecule, for example, sodiumlauryl sulfate, sodium secondary alkyl sulfates, sodium salts ofsulfonated castor oil, and sodium alkylaryl sulfonates such as sodiumdodecylbenzene sulfonate; and polymers of ethylene oxide and copolymersof ethylene oxide and propylene oxide.

The compositions of the invention may, for example, be formulated aswettable powders, dusts, granules, solutions, emulsifiable concentrates,emulsions, suspension concentrates and aerosols. Wettable powdersusually contain 25, 50 and 75%w of active ingredient and usuallycontain, in addition to solid inert carrier, 3-10%w of a dispersingagent and, where necessary, 0-10%w of stabilizer(s) and/or otheradditives such as penetrants or stickers. Dusts are usually formulatedas a dust concentrate having a similar composition to that of a wettablepowder but without a dispersant, and are diluted in the field withfurther solid carrier to give a composition usually containing 0.5-10%wof active ingredient. Granules are usually prepared to have a sizebetween 10 and 100 BS mesh (1.676-0.152 mm), and may be manufactured byagglomeration or impregnation techniques. Generally, granules willcontain 0.5-25%w active ingredient and 0-10%w of additives such asstabilizers, slow-release modifiers and binding agents. Emulsifiableconcentrates usually contain, in addition to a solvent and, whennecessary, co-solvent, 10-50%w/v active ingredient, 2-20%w/v emulsifiersand 0-20%w/v of other additives such as stabilizers, penetrants andcorrosion inhibitors. Suspension concentrates are usually compounded soas to obtain a stable, non-sedimenting flowable product and usuallycontain 10-75%w active ingredient, 0.5-15%w of dispersing agents,0.1-10%w of suspending agents such as protective colloids andthixotropic agents, 0-10%w of other additives such as defoamers,corrosion inhibitors, stabilizers, penetrants and stickers, and water oran organic liquid in which the active ingredient is substantiallyinsoluble; certain organic solids or inorganic salts may be presentdissolved in the formulation to assist in preventing sedimentation or asantifreeze agents for water.

Aqueous dispersions and emulsions, for example, compositions obtained bydiluting a wettable powder or a concentrate according to the inventionwith water, also lie within the scope of the present invention. The saidemulsions may be of the water-in-oil or of the oil-in-water type, andmay have a thick "mayonnaise"-like consistency.

Typical individual compounds of the invention have been prepared asdescribed in the following examples. In each case, the identity of theproduct was confirmed by appropriate chemical and spectral analyses.

EXAMPLE 1 4-Chloro-(3'-pyridyl)imino-C-(isopropylthio)methylbenzene (1)

A stirred mixture of 7 g of N-(3'-pyridyl)-4-chlorobenzamide and 22.5 mlof thionyl chloride was heated under reflux for two hours. Excessthionyl chloride was evaporated under reduced pressure, and the residue,4-chloro-(3'-pyridyl)imino-C-(chloro)methylbenzene, was treated with 100ml of dry pyridine. 4.5 g of isopropyl mercaptan was added and themixture was stirred and heated at 100°-100° C. for 16 hours. The solventand other volatile components of the mixture were evaporated underreduced pressure, and the residue was extracted with diethyl ether. Theextract was washed with water and dried over anhydrous magnesiumsulfate. After evaporation of the ether, the residue was subjected tochromatography on a silica gel column, eluting with diethyl ether/hexane(1:1 v:v), to give 1, as a yellow solid, m.p. 55.5°-57° C.

EXAMPLES 2 TO 15

By similar methods were prepared the compounds listed in Table I.

                  TABLE I                                                         ______________________________________                                         ##STR4##                                                                     Example                                                                              Compound                       mp                                      No.    No.       X              (Y).sub.m                                                                           °C.                              ______________________________________                                        2      2         S(CH.sub.2).sub.3 CH.sub.3                                                                   4-Cl  oil                                     3      3         SCH(CH.sub.3)CH.sub.2 CH.sub.3                                                               "     oil                                     4      4         SCH.sub.2 CH.sub.2 CH.sub.3                                                                  "     oil                                     5      5         SC(CH.sub.3).sub.3                                                                           "     97                                      6      6         SCH.sub.2 CH(CH.sub.3).sub.2                                                                 "     oil                                     7      7         S(CH.sub.3).sub.3                                                                            2,4-Cl.sub.2                                                                        90                                      8      8           "            3,4-Cl.sub.2                                                                        84-86                                   9      9         SCH.sub.2 CH(CH.sub.3).sub.2                                                                 2,4-Cl.sub.2                                                                        oil                                     10     10        SC.sub.3 H.sub.7                                                                             2,4-Cl.sub.2                                                                        oil                                     11     11        SC(CH.sub.3).sub.3                                                                           4-F   53                                      12     12        SCH(CH.sub.3).sub.2                                                                          2,4-Cl.sub.2                                                                        43-4                                    13     13        SCH(CH.sub.3)CH.sub.2 CH.sub.3                                                               "     oil                                     ______________________________________                                    

Fungicidal Activity

To illustrate the fungicidal activity of compounds of the invention, theexamples given hereinafter of a wide range of compounds of Formula I andrepresentative of the scope thereof include results obtained bysubjecting these compounds to a variety of tests representative of thespectrum of fungus species against which fungicidal compositions arerequired for use. The following tests were carried out:

(1) Activity against vine downy mildew (plasmopara viticola-P.v.-a.)

The test was a direct antisporulant one using a foliar spray. The lowersurfaces of leaves of whole vine plants were inoculated by spraying withan aqueous suspension containing 10⁵ zoosporangia per milliliter 4 daysprior to treatment with the test compound. The inoculated plants werekept for 24 hours in a high humidity compartment, 48 hours at glasshouseambient temperature and humidity and then returned for a further 24hours to high humidity. The plants then were dried and infected leavesdetached and sprayed on the lower surfaces at a dosage of 1 kilogram ofactive material per hectare using a track sprayer. After drying, thepetioles of the sprayed leaves were dipped in water and the leavesreturned to high humidity for a further 72 hours incubation, followed byassessment. Assessment was based on the percentage of the leaf areacovered by sporulation compared with that on control leaves.

(2) Activity against vine downy mildew (Plasmopara viticola-P.v.-t.)

The test was a translaminar protectant one using a foliar spray. Theupper surfaces of leaves of whole vine plants were sprayed at a dosageof 1 kilogram of active material per hectare using a track sprayer. Thelower surfaces of the leaves were then inoculated, up to 6 hours aftertreatment with the test compound, by spraying with an aqueous suspensioncontaining 10⁵ zoosporangia per milliliter. The inoculated plants werekept for 24 hours in a high humidity compartment, 4 days at glasshouseambient temperature and humidity and then returned for a further 24hours to high humidity. Assessment was based on the percentage of theleaf area covered by sporulation compared with that on control leaves.

(3) Activity against vine grey mold (Botrytis cinerea-B.c.)

The test was a direct eradicant one using a foliar spray. Theunder-surfaces of detached vine leaves were inoculated by pipetting 10large drops of an aqueous suspension containing 5×10⁵ conidia permilliliter onto them. The inoculated leaves were kept uncoveredovernight during which time the drops containing the conidia slowlydried. By this time the fungus had penetrated the leaf and a visiblenecrotic lesion sometimes was apparent where the drop was made. Theinfected regions were sprayed directly with a dosage of one kilogram ofactive material per hectare using a track sprayer. When the spray haddried the leaves were covered with petri dish lids and the diseaseallowed to develop under the moist conditions. The extent of thenecrotic lesion beyond the original drop together with the degree ofsporulation was compared with that on control leaves.

(4) Activity against potato late blight (Phytophthora infestans-P.i.-e.)

The test was a direct eradicant one using a foliar spray. The uppersurfaces of the leaves of potato plants (12-18 centimeters high, inmonopots) were inoculated by spraying with an aqueous suspensioncontaining 5×10³ zoosporangia per milliliter 16-19 hours prior totreatment with the test compound. The inoculated plants were keptovernight at high humidity and then allowed to dry before spraying at adosage of 1 kilogram of active material per hectare using a tracksprayer. After spraying, the plants were returned to high humidity for afurther period of 48 hours. Assessment was based on a comparison betweenthe levels of disease on the treated and control plants.

(5) Activity against potato late blight (Phytophthora infestans-P.i.-p.)

The test measured the direct protectant activity of compounds applied asa foliar spray. Tomato plants, cultivar Ailsa Craig, 1-15 cms high, inmonopots were used. The whole plant was sprayed at a dosage of 1kilogram of active material per hectare using a track sprayer. The plantthen was inoculated up to 6 hours after treatment with the testcompound, by spraying with an aqueous suspension containing 5×10³zoosporangia per milliliter. The inoculated plants were kept in highhumidity for 3 days. Assessment was based on a comparison between thelevels of disease on the treated and control plants.

(6) Activity against barley powdery mildew (Erysiphe graminis-E.g.)

The test measured the direct antisporulant activity of compounds appliedas a foliar spray. For each compound about 40 barley seedlings weregrown to the one-leaf stage in a plastic pot of sterile potting compost.Inoculation was effected by dusting the leaves with conidia of Erysiphegraminis spp. hordei. Twenty-four hours after inoculation the seedlingswere sprayed with a solution of the compound in a mixture of acetone(50%), surfactant (0.049%) and water using a track sprayer. The rate ofapplication was equivalent to 1 kilogram of active material per hectare.First assessment of disease was made 5 days after treatment, when theoverall level of sporulation on the treated pots was compared with thaton control pots.

(7) Acitivity against wheat brown rust (Puccinia recondita-P.r.)

The test was a direct antisporulant one using a foliar spray. Potscontaining about 25 wheat seedlings per pot, at first leaf stage, wereinoculated by spraying the leaves with an aqueous suspension, containing10⁵ spores per milliliters plus a little Triton X-155, 20-24 hoursbefore treatment with the compound under test. The inoculated plantswere kept overnight in a high humidity compartment, dried at glasshouseambient temperature and then sprayed at a dosage of 1 kilogram of activematerial per hectare using a track sprayer. After treatment, the plantswere kept at glasshouse ambient temperature and assessment made about 11days after treatment. Assessment was based on the relative density ofsporulating pustules per plant compared with that on control plants.

(8) Activity against broad bean rust (Uromyces fabae-U.f.)

The test was a translaminar antisporulant one using foliar spray. Potscontaining one plant per pot were inoculated by spraying an aqueoussuspension, containing 5×10⁴ spores per milliliter plus a little TritonX-155, onto the undersurface of each leaf 20-24 hours before treatmentwith test compound. The inoculated plants were kept overnight in a highhumidity compartment, dried at glasshouse ambient temperature and thensprayed on the leaf upper surface, at a dosage of one kilogram perhectare of active material using a track sprayer. After treatment theplants were kept at glasshouse temperature and assessment made 11-14days after treatment. Symptoms were assessed on the relative density ofsporulating pustules per plant compared with that on control plants.

(9) Activity against rice leaf blast (Pyricularia oryzae-P.o.)

The test was a direct eradicant one using a foliar spray. The leaves ofrice seedlings (about 30 seedlings per pot) were sprayed with an aqueoussuspension containing 10⁵ spores per milliliter 20-24 hours prior totreatment with the test compound. The inoculated plants were keptovernight in high humidity and then allowed to dry before spraying at adosage of 1 kilogram of active material per hectare using a tracksprayer. After treatment, the plants were kept in a rice compartment at25°-30° C. and high humidity. Assessments were made 4-5 days aftertreatment and were based on the density of necrotic lesions and thedegree of withering when compared with control plants.

(10) Activity against rice sheath blight (Pellicularia sasakii-P.s.)

The test was a direct eradicant one using foliar spray. 20-24 hoursprior to treatment with the test compound, rice seedlings (about 30seedlings per pot) were sprayed with 5 milliters of an aqueoussuspension containing 0.2 gram of crushed sclerotia/mycelium permilliliter. The inoculated plants were kept overnight in a humid cabinetmaintained at 25°-30° C., followed by spraying at a dosage of 1 kilogramof active material per hectare. The treated plants then were returned tohigh humidity for a further period of 3-4 days. With this disease brownlesions were seen that started at the base of the sheath and extendedupwards. Assessments were made on the number and extent of the lesionswhen compared with the controls.

(11) Activity against apple powdery mildew (Podospmaeraleucotricha-P.l.)

The test was a direct anti-sporulant one using a foliar spray. The uppersurfaces of leaves of whole apple seedlings were inoculated by sprayingwith an aqueous suspension containing 10⁵ conidia per milliliter 2 daysprior to treatment with the test compound. The inoculated plants wereimmediately dried and kept at glasshouse ambient temperatures andhumidity prior to treatment. The plants were sprayed at a dosage of 1kilogram of active material per hectare using a track sprayer. Afterdrying the plants were returned to a compartment at ambient temperatureand humidity for up to 9 days, followed by assessment. Assessment wasbased on the percentage of the leaf area covered by sporulation comparedwith that on leaves of control plants.

(12) Activity against peanut leaf spot (Cercopsora arachidicola-C.a.)

The test was a direct eradicant one using a foliar spray. The uppersurfaces of the leaves of peanut plants (12-20 centimeters high, inmonopots) were inoculated by spraying with an aqueous suspensioncontaining 10⁵ conidia per milliter 40-43 hours prior to treatment withthe test compound. The inoculated plants were kept at high humidity andthen allowed to dry during the interval between inoculation andtreatment by spraying at a dosage of 1 kilogram of active material perhectare using a track sprayer. After spraying, the plants were moved toa humid compartment at 25°-28° C. for a further period of up to 10 days.Assessment was based on a comparison between the levels of disease onthe treated and control plants.

In these tests, compounds 2 through 14 were not tested with respect tothe organisms: P.o. and P.s., compounds 1-14 were not tested withrespect to the organisms: P.l. and C.a., and compounds 15-36 were nottested with respect to the organism: P.s.

The extent of disease control was expressed as a control ratingaccording to the criteria:

0=less than 50% disease control

1=50-80% disease control

2=greater than 80% disease control PG,15

The disease control ratings are given in Table II for the compoundsdescribed in the previous Examples.

                  TABLE II                                                        ______________________________________                                                    Compounds having the Rating*                                      Organism      2            1                                                  ______________________________________                                        P.v.-a.                                                                       P.v.-t.       1,9          22,23                                              B.c.          7,13                                                            P.i.-e.                                                                       P.i.-p.       10           4                                                  E.g.          1,2,3,4,5,6,                                                                  7,9,10,12                                                       P.r.          7            5 (systemic),                                                                 21,22                                              U.f.          7,9                                                             P.o.                       1                                                  P.s.          1                                                               P.l.          7,8,9,10,11                                                     C.a.          7,9,10       8                                                  ______________________________________                                         *Otherwise the test compounds had a "0" rating with respect to the            organisms.                                                               

We claim:
 1. A compound of the formula ##STR5## wherein X is alkylthioof from one to six carbon atoms; m is 1 or 2; and Y is halogen, andacid-addition salts thereof.
 2. A compound according to claim 1 whereinY is chlorine.
 3. A compound according to claim 2 wherein m is one andthe chlorine atom is bonded to the carbon atom in the para-position ofthe ring.
 4. A fungicidal composition comprising a fungicidallyeffective amount of a compound of claim 1 in association with at leastone inert carrier thereof.
 5. A method of protecting a crop from fungalattack comprising treating crops subject to or subjected to fungalattack, seeds of such crops or soil in which such crops are growing orare to be grown with a fungicidally effective amount of a compoundaccording to claim 1, or a composition according to claim
 4. 6. Afungicidal composition comprising a fungicidally effective amount of acompound of claim 2 in association with at least one inert carriertherefor.
 7. A method of protecting a crop from fungal attack comprisingtreating crops subject to or subjected to fungal attack, seeds of suchcrops or soil in which such crops are growing or are to be grown with afungicidally effective amount of a compound according to claim 2.